tbuckley/cabot-search huggingface dataset:
Head-to-Head Comparison of 18F-FDG and 68Ga-FAPI-04 PET/CT for Radiological Evaluation of Cervical Cancer
Authors: Qiaoqiao Shu, Xubing He, Xi Chen, Mengna Liu, Yue Chen, Liang Cai
Journal: Clinical Nuclear Medicine (2023)

We aimed to compare the potential value of 68 Ga-FAPI-04 and 18 F-FDG PET/CT in primary cervical cancer and lymph node metastases.Patients with cervical cancer underwent both 68 Ga-FAPI-04 and 18 F-FDG PET/CT. Histopathology and follow-up CT or MRI results (at least 3 months of follow-up) were used as reference criteria. Paired-sample t test was used to compare the SUV max of 18 F-FDG and 68 Ga-FAPI-04 PET/CT for cervical cancer primary lesions and metastatic lymph nodes.A total of 35 patients with a mean age of 53 ± 11 years (range, 30-76 years) were included. The detection rate of both tracers for primary tumors was 100%. There was no significant correlation between 18 F-FDG and 68 Ga-FAPI-04 for SUV max (14.5 ± 5.7 vs 15.1 ± 6.2; P = 0.645). In addition, the detection rates of 68 Ga-FAPI-04 and 18 F-FDG for lymph node metastasis were 100% and 98%, respectively. No significant difference was found in SUV max between 18 F-FDG and 68 Ga-FAPI-04 groups (7.6 ± 4.0 vs 7.0 ± 3.5; P = 0.572). Twelve false-positive lymph nodes were detected in 8 patients with 18 F-FDG PET/CT, none of which were developed on 68 Ga-FAPI-04 PET/CT.68 Ga-FAPI-04 PET/CT has a high tracer rate for the diagnosis of primary cervical cancer and lymph node metastases. Moreover, 68 Ga-FAPI-04 PET/CT also showed good results in distinguishing metastatic lymph nodes from reactive lymph nodes of cervical cancer.
Increased Uptake in Microcystic Serous Cystadenoma Mimicking Pancreatic Neuroendocrine Tumor on 68Ga-DOTATATE PET/MRI
Authors: Jing Gao, Chang Liu, Jinxin Zhou, Xiaozhu Lin, Yifan Zhang
Journal: Clinical Nuclear Medicine (2023)

Abstract A 2.6-cm solid cystic lesion in the pancreatic head was found in a 51-year-old woman on CT. A pancreatic neuroendocrine tumor was suspected, and a 68 Ga-DOTATATE PET/MRI was performed, which showed increased tracer uptake in the lesion. However, postsurgical pathologic examination indicated a pancreatic serous cystadenoma. Here, we reported a case of microcystic pancreatic serous cystadenoma that could be misdiagnosed as a pancreatic neuroendocrine tumor on a 68 Ga-DOTATATE PET/MRI.
Somatostatin Receptor–Directed PET/CT Can Differentiate Between Different Subtypes of Head and Neck Paragangliomas
Authors: Yingjun Zhi, Elena Gerhard-Hartmann, Philipp E. Hartrampf, Alexander Weich, Takahiro Higuchi, Thorsten A. Bley, Stephan Hackenberg, Rudolf Hagen, Andreas Rosenwald, Agmal Scherzad, Hanna Remde, Martin Fassnacht, Rudolf A. Werner, Sebastian E. Serfling
Journal: Clinical Nuclear Medicine (2023)

Given their neuroendocrine origin, head and neck paragangliomas (HNPGLs) can be imaged with somatostatin receptor (SSTR)-directed PET/CT. We aimed to determine whether the in vivo PET signal can differentiate between varying HNPGL subtypes.Fourteen patients with HNPGL received pretherapeutic SSTR-PET/CTs using 68 Ga-DOTATOC. Six (42.9%) patients had a jugular paraganglioma (PGL-J), 5 (35.7%) were diagnosed with carotid paraganglioma (PGL-Cs), and the remaining 3 patients (21.4%) had PGL-C with pathogenic SDHx germline variants (PGL-C-SDH). A visual and quantitative assessment of the primary tumor on SSTR-PET was performed, including SUV max and target-to-background ratio (TBR). Quantitative values were then compared between subgroups of patients affected with different HNPGL entities.On visual assessment, all primary HNPGLs could be identified on SSTR-PET/CT. Quantification of HNPGL revealed substantially elevated SUV max in PGL-J (101.7 ± 58.5) when compared with PGL-C-SDH (13.4 ± 5.6, P < 0.05), but not when compared with PGL-C (66.7 ± 27.3, P = 0.4; PGL-C vs PGL-C-SDH, P = 0.2). TBR of PGL-J (202.9 ± 82.2), however, further differentiated between PGL-C (95.7 ± 45.4, P < 0.05) and PGL-C-SDH (20.4 ± 12.2, P < 0.01; PGL-C vs PGL-C-SDH, P = 0.3). Moreover, whole-body readout revealed metastases in 2/3 (66.7%) of PGL-C-SDH patients, with a single SSTR-expressing skeletal lesion in one subject and bipulmonary lesions in the other patient.In patients with HNPGL, SSTR-PET/CT identified the primary and metastatic disease and provides substantially elevated TBR, indicating excellent image contrast. PET-based quantification can also differentiate between varying HNPGL subtypes.
Dynamic CZT-SPECT
Authors: Matthieu Bailly, Maxime Courtehoux, Gilles Metrard, Denis Angoulvant, Maria Joao Ribeiro
Journal: Clinical Nuclear Medicine (2023)

Abstract CZT-SPECT myocardial perfusion enables quantification of myocardial blood flow (MBF). Normal values and thresholds have been accurately defined in PET but remain unclear in SPECT. The aim of this study was to report normal MBF and myocardial flow reserve values in very low-risk patients referred for coronary artery disease screening with dynamic SPECT, in comparison with patients experiencing coronary artery disease. Eighty-four patients (31 male) were analyzed. The mean 10 years risk of fatal cardiovascular events score was 2.7% ± 1.4%. The mean global stress MBF and myocardial flow reserve were 1.6 ± 0.6 mL/min/g and 2.7 ± 0.7.
Secreted folate receptor γ drives fibrogenesis in metabolic dysfunction–associated steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells
Authors: Connor Quinn, Mario C. Rico, Carmen Merali, Carlos A. Barrero, Oscar Perez-Leal, Victoria Mischley, John Karanicolas, Scott L. Friedman, Salim Merali
Journal: Science Translational Medicine (2023)

Hepatic fibrosis is the primary determinant of mortality in patients with metabolic dysfunction–associated steatohepatitis (MASH). Transforming growth factor–β (TGFβ), a master profibrogenic cytokine, is a promising therapeutic target that has not yet been translated into an effective therapy in part because of liabilities associated with systemic TGFβ antagonism. We have identified that soluble folate receptor γ (FOLR3), which is expressed in humans but not in rodents, is a secreted protein that is elevated in the livers of patients with MASH but not in those with metabolic dysfunction–associated steatotic liver disease, those with type II diabetes, or healthy individuals. Global proteomics showed that FOLR3 was the most highly significant MASH-specific protein and was positively correlated with increasing fibrosis stage, consistent with stimulation of activated hepatic stellate cells (HSCs), which are the key fibrogenic cells in the liver. Exposure of HSCs to exogenous FOLR3 led to elevated extracellular matrix (ECM) protein production, an effect synergistically potentiated by TGFβ1. We found that FOLR3 interacts with the serine protease HTRA1, a known regulator of TGFBR, and activates TGFβ signaling. Administration of human FOLR3 to mice induced severe bridging fibrosis and an ECM pattern resembling human MASH. Our study thus uncovers a role of FOLR3 in enhancing fibrosis.
Diagnostic Utility of 99mTc-MDP Bone Scintigraphy for Nivolumab-Induced Inflammatory Arthritis
Authors: Yoshihiro Araki, Tomonori Misaki, Yasuhiro Ueda, Naoyuki Matsumoto, Yuji Takaso
Journal: Clinical Nuclear Medicine (2023)

Abstract Immune checkpoint inhibitors can revive exhausted helper T-cells, and inflammatory cell reactivation may cause autoimmune disease–like conditions. Drug-induced arthritis is an immune-related adverse event, but the diagnostic approach is undefined. We present the diagnostic utility of 99m Tc-MDP bone scintigraphy for nivolumab-induced inflammatory arthritis. A 67-year-old man with hypopharyngeal carcinoma presented bilateral multiple metacarpophalangeal joint pain and swelling at each nivolumab administration. Regular imaging findings were atypical for inflammatory arthritis and did not fulfill the criteria for rheumatoid arthritis. We diagnosed nivolumab-induced inflammatory arthritis based on clinical symptoms and the symmetrical moderate uptake of the affected joints on 99m Tc-MDP bone scintigraphy.
Body Composition, Coronary Microvascular Dysfunction, and Future Risk of Cardiovascular Events Including Heart Failure
Authors: Ana Carolina do A.H. Souza, Michael H. Rosenthal, Filipe A. Moura, Sanjay Divakaran, Michael T. Osborne, Jon Hainer, Sharmila Dorbala, Ron Blankstein, Marcelo F. Di Carli, Viviany R. Taqueti
Journal: JACC. Cardiovascular imaging (2023)
A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus
Authors: Longping V. Tse, Yixuan J. Hou, Elizabeth McFadden, Rhianna E. Lee, Trevor D. Scobey, Sarah R. Leist, David R. Martinez, Rita M. Meganck, Alexandra Schäfer, Boyd L. Yount, Teresa Mascenik, John M. Powers, Scott H. Randell, Yi Zhang, Lingshu Wang, John Mascola, Jason S. McLellan, Ralph S. Baric
Journal: Science Translational Medicine (2023)

The repeated emergence of zoonotic human betacoronaviruses (β-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)–related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV/ li /GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/M pro protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV–neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo–electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development.
Could 68Ga-DOTA-UBI-29-41 Help Identify Chronic Osteomyelitis on PET/CT Images? A Pilot Study
Authors: Solange Amorim Nogueira, Marycel F. de Barboza, Adriana M. Dell’Aquila, Durval C. B Santos, Akemi Osawa
Journal: Clinical Nuclear Medicine (2023)

This pilot study aimed to confirm the presence of infectious agents in infection foci using PET/CT imaging with 68 Ga-DOTA-UBI (29-41) in 7 patients with chronic osteomyelitis and with indications for surgical cleaning at the site of the infection focus. The whole-body PET/CT was performed on Biograph mCT 40 PET/CT scanner (Siemens Healthineers); the image began 45-60 minutes postinjection of the radiotracer (148-260 MBq). This study demonstrated that, in 6 patients in whom the PET/CT was classified as positive for identified infectious foci, confirmed by culture of the secretion sample collected during surgery, only 1 patient in antibiotic therapy was negative.
Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch
Authors: Zhi Luo, David Klein Cerrejon, Simon Römer, Nicole Zoratto, Jean-Christophe Leroux
Journal: Science Translational Medicine (2023)

Biopharmaceuticals, including proteins and peptides, have revolutionized the treatment of a wide range of diseases, from diabetes and cardiovascular disorders to virus infections and cancer. Despite their efficacy, most of these macromolecular drugs require parenteral administration because of their high molecular weight and relative instability. Over the past 40 years, only a few oral peptide drugs have entered clinical trials, even when formulated with substantial amounts of permeation enhancers. To overcome the epithelial barrier, devices that inject drugs directly into the gastrointestinal mucosa have been proposed recently. However, the robustness and safety of those complex systems are yet to be assessed. In this study, we introduced an innovative technology to boost drug absorption by synergistically combining noninvasive stretching of the buccal mucosa with permeation enhancers. Inspired by the unique structural features of octopus suckers, a self-applicable suction patch was engineered, enabling strong adhesion to and effective mechanical deformation of the mucosal tissue. In dogs, this suction patch achieved bioavailability up to two orders of magnitude higher than those of the commercial tablet formulation of desmopressin, a peptide drug known for its poor oral absorption. Moreover, systemic exposure comparable to that of the approved oral semaglutide tablet was achieved without further optimization. Last, a first-in-human study involving 40 healthy participants confirmed the dosage form’s acceptability, thereby supporting the clinical translatability of this simple yet effective platform technology.
Targeting ryanodine receptor type 2 to mitigate chemotherapy-induced neurocognitive impairments in mice
Authors: Yang Liu, Steven Reiken, Haikel Dridi, Qi Yuan, Khalid S. Mohammad, Trupti Trivedi, Marco C. Miotto, Kaylee Wedderburn-Pugh, Leah Sittenfeld, Ynez Kerley, Jill A. Meyer, Jonathan S. Peters, Scott C. Persohn, Amanda A. Bedwell, Lucas L. Figueiredo, Sukanya Suresh, Yun She, Rajesh Kumar Soni, Paul R. Territo, Andrew R. Marks, Theresa A. Guise
Journal: Science Translational Medicine (2023)

Chemotherapy-induced cognitive dysfunction (chemobrain) is an important adverse sequela of chemotherapy. Chemobrain has been identified by the National Cancer Institute as a poorly understood problem for which current management or treatment strategies are limited or ineffective. Here, we show that chemotherapy treatment with doxorubicin (DOX) in a breast cancer mouse model induced protein kinase A (PKA) phosphorylation of the neuronal ryanodine receptor/calcium (Ca2+) channel type 2 (RyR2), RyR2 oxidation, RyR2 nitrosylation, RyR2 calstabin2 depletion, and subsequent RyR2 Ca2+ leakiness. Chemotherapy was furthermore associated with abnormalities in brain glucose metabolism and neurocognitive dysfunction in breast cancer mice. RyR2 leakiness and cognitive dysfunction could be ameliorated by treatment with a small molecule Rycal drug (S107). Chemobrain was also found in noncancer mice treated with DOX or methotrexate and 5-fluorouracil and could be prevented by treatment with S107. Genetic ablation of the RyR2 PKA phosphorylation site (RyR2-S2808A) also prevented the development of chemobrain. Chemotherapy increased brain concentrations of the tumor necrosis factor-α and transforming growth factor-β signaling, suggesting that increased inflammatory signaling might contribute to oxidation-driven biochemical remodeling of RyR2. Proteomics and Gene Ontology analysis indicated that the signaling downstream of chemotherapy-induced leaky RyR2 was linked to the dysregulation of synaptic structure-associated proteins that are involved in neurotransmission. Together, our study points to neuronal Ca2+ dyshomeostasis via leaky RyR2 channels as a potential mechanism contributing to chemobrain, warranting further translational studies.
Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis
Authors: Meghan Mooring, Grace A. Yeung, Panu Luukkonen, Silvia Liu, Muhammad Waqas Akbar, Gary J. Zhang, Oluwashanu Balogun, Xuemei Yu, Rigen Mo, Kari Nejak-Bowen, Masha V. Poyurovsky, Carmen J. Booth, Liza Konnikova, Gerald I. Shulman, Dean Yimlamai
Journal: Science Translational Medicine (2023)

Obesity is increasing worldwide and leads to a multitude of metabolic diseases, including cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis (NASH). Cysteine-rich angiogenic inducer 61 (CYR61) is associated with the progression of NASH, but it has been described to have anti- and proinflammatory properties. We sought to examine the role of liver CYR61 in NASH progression. CYR61 liver-specific knockout mice on a NASH diet showed improved glucose tolerance, decreased liver inflammation, and reduced fibrosis. CYR61 polarized infiltrating monocytes promoting a proinflammatory/profibrotic phenotype through an IRAK4/SYK/NF-κB signaling cascade. In vitro, CYR61 activated a profibrotic program, including PDGFa/PDGFb expression in macrophages, in an IRAK4/SYK/NF-κB–dependent manner. Furthermore, targeted-antibody blockade reduced CYR61-driven signaling in macrophages in vitro and in vivo, reducing fibrotic development. This study demonstrates that CYR61 is a key driver of liver inflammation and fibrosis in NASH.
Sustained Improvement of Cystic Fibrosis Lung Disease following Initiation of Elexacaftor/Tezacaftor/Ivacaftor Therapy: Lessons from Real-World Studies
Authors: Eva Steinke, Mirjam Stahl
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Sustained Improvement of Cystic Fibrosis Lung Disease Following Initiation of Elexacaftor/Tezacaftor/Ivacaftor Therapy: Lessons from Real-World Studies." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Clinical Outcomes Based on Coronary Computed Tomography-Derived Fractional Flow Reserve and Plaque Characterization
Authors: Yoshihiro Sato, Sadako Motoyama, Keiichi Miyajima, Hideki Kawai, Masayoshi Sarai, Takashi Muramatsu, Hiroshi Takahashi, Hiroyuki Naruse, Amir Ahmadi, Yukio Ozaki, Hideo Izawa, Jagat Narula
Journal: JACC. Cardiovascular imaging (2023)
Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort
Authors: Axelle Mabo, Raphael Borie, Lidwine Wemeau-Stervinou, Yurdagül Uzunhan, Emmanuel Gomez, Gregoire Prevot, Martine Reynaud-Gaubert, Julie Traclet, Emmanuel Bergot, Jacques Cadranel, Sylvain Marchand-Adam, Anne Bergeron, Elodie Blanchard, Benjamin Bondue, Philippe Bonniaud, Arnaud Bourdin, Pierre Regis Burgel, Sandrine Hirschi, Charles Hugo Marquette, Sébastien Quétant, Hilario Nunes, Cécile Chenivesse, Bruno Crestani, Yoann Guirriec, Delphine Monnier, Cédric Ménard, Pierre Tattevin, Vincent Cottin, David Luque Paz, Stéphane Jouneau
Journal: Thorax (2023)

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.
Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy
Authors: Colm J O'Rourke, Massimiliano Salati, Colin Rae, Guido Carpino, Holly Leslie, Antonio Pea, Maria G Prete, Luca R Bonetti, Francesco Amato, Robert Montal, Rosie Upstill-Goddard, Colin Nixon, Paula Sanchon-Sanchez, Paolo Kunderfranco, Daniela Sia, Eugenio Gaudio, Diletta Overi, Stefano Cascinu, Dan Hogdall, Sian Pugh, Enric Domingo, John N Primrose, John Bridgewater, Andrea Spallanzani, Fabio Gelsomino, Josep M Llovet, Diego F Calvisi, Luke Boulter, Francesco Caputo, Ana Lleo, Nigel B Jamieson, Gabriele Luppi, Massimo Dominici, Jesper B Andersen, Chiara Braconi
Journal: Gut (2023)

Objective Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that the pretreatment molecular profiles of diagnostic biopsies can predict patient benefit from chemotherapy and define molecular bases of innate chemoresistance. Design We identified a cohort of advanced iCCA patients with comparable baseline characteristics who diverged as extreme outliers on chemotherapy (survival &lt;6 m in rapid progressors, RP; survival &gt;23 m in long survivors, LS). Diagnostic biopsies were characterised by digital pathology, then subjected to whole-transcriptome profiling of bulk and geospatially macrodissected tissue regions. Spatial transcriptomics of tumour-infiltrating myeloid cells was performed using targeted digital spatial profiling (GeoMx). Transcriptome signatures were evaluated in multiple cohorts of resected cancers. Signatures were also characterised using in vitro cell lines, in vivo mouse models and single cell RNA-sequencing data. Results Pretreatment transcriptome profiles differentiated patients who would become RPs or LSs on chemotherapy. Biologically, this signature originated from altered tumour-myeloid dynamics, implicating tumour-induced immune tolerogenicity with poor response to chemotherapy. The central role of the liver microenviroment was confrmed by the association of the RPLS transcriptome signature with clinical outcome in iCCA but not extrahepatic CCA, and in liver metastasis from colorectal cancer, but not in the matched primary bowel tumours. Conclusions The RPLS signature could be a novel metric of chemotherapy outcome in iCCA. Further development and validation of this transcriptomic signature is warranted to develop precision chemotherapy strategies in these settings.
Core outcome set for pulmonary rehabilitation of patients with COPD: results of a modified Delphi survey
Authors: Sara Souto-Miranda, Isabel Saraiva, Martijn A Spruit, Alda Marques
Journal: Thorax (2023)

Introduction There is high heterogeneity of outcomes and measures reported in pulmonary rehabilitation (PR) trials of people with chronic obstructive pulmonary disease (COPD). This hinders study comparability and benchmarking of PR. We have developed a core outcome set (COS) to overcome these challenges. Methods This study was informed by a systematic review and two qualitative studies and had patient involvement since its inception. A two-round Delphi survey was available in seven languages. Outcomes (n=63) scored 7–9 (crucial) by ≥70% of the participants and 1–3 (not that important) by ≤15% of participants from both groups in the Likert scale were automatically included in the COS, while outcomes that were considered crucial by only one of the groups were further discussed by the authors in a meeting. Results A total of 299 people (n=229 healthcare professionals/researchers/policy-makers; n=70 people with COPD and informal caregivers) participated in the survey (83% retention), which covered 29 countries/five continents. After the second round, six outcomes were included and three were added in the meeting. The final COS contains dyspnoea, fatigue, functional exercise capacity, health-related quality of life, health behaviours/lifestyle, knowledge about the disease, lower limb muscle function, personal goals and problematic activities of daily living. Conclusion A COS for PR of people with COPD is now available and can be used by different stakeholders to improve consistency and comparability of studies, benchmark PR and improve the quality of care provided. Future research should establish the core measures and investigate the uptake of this COS.